Sheila Singh, Director of the Centre for Discovery in Cancer Research (CDCR) at McMaster University, shared a post on LinkedIn:
“I’m delighted to share news of our Nature publication out today which describes on a novel CAR‑T strategy for glioblastoma (GBM).
GBM remains one of the most aggressive cancers, with 96% of patients dying within 5 years, and CAR‑T therapy has yet to deliver true benefit in this disease. So, we asked a different question: What if we target not only tumour cells, but also the local immune cells?
First, we found that local macrophages – which can make up to 40% of the tumour mass – help create an immune-suppressive environment around the tumour. We also found that GPNMB is present on both the GBM cells and the tumor-supporting macrophages. So, we made GPNMB-directed CAR-T cells and discovered their potent anti-tumour activity in preclinical models. Two doses of GPNMB-directed CAR-T completely cured diseased mice, including our patient-derived models!
This work introduces a new paradigm for treating GBM – we must target the tumour-immune ecosystem, not just the tumour. Corroborating evidence from Carl June and colleagues suggests GPNMB is a promising candidate not only for GBM, but is a top AI-nominated pan-cancer target for CAR-T cell therapy, as reported in Cell by Cell Press last week. I can’t wait to take these immunotherapies further at King’s College London and King’s Health Partners!
I’m extremely grateful to all collaborators, patients, and research teams who made this possible and to McMaster University, Brain Cancer Canada, Terry Fox Research Institute, Brain Canada, Cancer Research Society, Canadian Institutes of Health Research | Instituts de recherche en santé du Canada, Brain Tumour Foundation of Canada, Lotte & John Hecht Memorial Foundation for supporting this work.”
Title: Dual tumour–myeloid targeting of glioblastoma with GPNMB CAR-T cells
Authors: Neil Savage, Shan Grewal, Muhammad Vaseem Shaikh, Franz J. Zemp, Dillon Mckenna, Nicholas Mikolajewicz, Hinda Najem, Joanna Pyczek, Jiuran Wei, Mohamed A. B. Taleb, Lucas C. Asselstine, Alisha Anand, Shawn C. Chafe, Kui Zhai, William T. Maich, Chirayu R. Chokshi, Hardikkumar Patel, Tiegan E. Korman, Minomi Subapanditha, Zoya Tabunshchyk, Nazanin Tatari, Petar Miletic, David Chen, Sebastian Pacheco, Sheila K. Singh
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